The kinetics of deuterated-homovanillic acid (HVA) were studied in untreated parkinsonian patients to provide an estimate of the central (brain) contribution to the total body production rate of HVA. The relative value of the level of HVA in CSF, blood and urine as index of brain dopamine metabolism was assessed. Biochemical studies of central and peripheral monoamine systems were carried out in patients with parkinsonism induced by NMPTP (N-methyl-4-phenyl 1-1,2,3,6-tetrahydrophridine). The clinical response of these patients to L-dopa and direct acting dopamine agonists was also studied. A new primate model of Parkinson's disease, the NMPTP-lesioned monkey, was developed. The neurochemical and neuropathological changes as well as the abnormal motor behavior produced by NMPTP in the monkey were described.